Mysterious ‘compound X’ clears toxic Parkinson’s proteins from brain

A mystery drug has shown promise for Parkinson’s disease, improving mobility and balance in mice with Parkinson’s-like symptoms. The drug works by stimulating the brain’s waste disposal system to remove clumps of toxic proteins, but the researchers behind the work have not yet revealed what the treatment is, referring to it only as Compound X.

“We aim to put some [intellectual property] protection around the reuse of Compound

Parkinson’s disease, which affects more than 10 million people worldwide, is associated with a loss of nerve cells in parts of the brain that help control movement. This is thought to be due to the accumulation of a misfolded form of a protein called alpha-synuclein. Studies suggest that this accumulates due to deficiencies in the brain’s waste disposal system, known as the glymphatic system. But it was unclear whether strengthening this system alleviated symptoms.

To explore this, Yan and his colleagues turned to a new mouse model of Parkinson’s disease. The approach, which they previously developed, involves repeatedly administering a few drops containing misfolded alpha-synuclein into the noses of mice. From there, the protein spreads in and around the brain, causing increasingly severe mobility problems. This replicates Parkinson’s disease much more accurately than other models in which symptoms are induced by brain damage, such as exposure to toxins, without replicating the clumps of alpha-synuclein we see in humans, Yan says. She presented the study results at the Oxford Glymphatic and Brain Clearance symposium in the United Kingdom on April 1.

The team exposed 20 mice to weekly doses of alpha-synuclein for four months. Two months later, half of the mice were given Compound X, a drug approved by the U.S. Food and Drug Administration, four times a week. This group also received a chemical called methylcellulose which helps the medicine dissolve. Compound

The remaining mice received methylcellulose alone, acting as controls. The degree to which Parkinson’s disease progressed in the mice was roughly equivalent to that of people with early-stage Parkinson’s disease, where they might experience changes in their smell or sleep, Yan says.

All mice then completed a mobility test in which they were placed on top of a thin pole and had to carefully turn their bodies to descend. In the compound group

Another movement task required mice to balance on a rotating rod for 5 minutes. Almost all of those given Compound

Further analysis revealed that Compound X stimulated slow brain waves during deep sleep, thereby improving fluid flow through the glymphatic system. It also reduced the number of alpha-synuclein clusters in the mice’s motor cortex – a region of the brain that controls movement – ​​by 40% more on average, compared to methylcellulose alone.

“I think it’s very important,” says Wenzhen Duan of Johns Hopkins University in Maryland. “We need compounds or therapies that can delay or slow the disease. Clinically available treatments temporarily relieve symptoms,” [but] none of them really slow or change the disease.

The team hopes to gain regulatory approval to test the drug in people with early-stage Parkinson’s disease within the next year. “The long-term goal would be to treat patients at the earliest phase of the disease, as this would provide the greatest benefit,” says Yan.